Complexity and algorithms for copy-number evolution problems

Background Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along...

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Veröffentlicht in:Algorithms for molecular biology Jg. 12; H. 1; S. 13 - 11
Hauptverfasser: El-Kebir, Mohammed, Raphael, Benjamin J., Shamir, Ron, Sharan, Roded, Zaccaria, Simone, Zehavi, Meirav, Zeira, Ron
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 16.05.2017
Springer Nature B.V
BMC
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ISSN:1748-7188, 1748-7188
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Zusammenfassung:Background Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along a chromosome constitutes the chromosome’s copy-number profile. Understanding how such profiles evolve in cancer can assist in both diagnosis and prognosis. Results We model the evolution of a tumor by segmental deletions and amplifications, and gauge distance from profile a to b by the minimum number of events needed to transform a into b . Given two profiles, our first problem aims to find a parental profile that minimizes the sum of distances to its children. Given k profiles, the second, more general problem, seeks a phylogenetic tree, whose k leaves are labeled by the k given profiles and whose internal vertices are labeled by ancestral profiles such that the sum of edge distances is minimum. Conclusions For the former problem we give a pseudo-polynomial dynamic programming algorithm that is linear in the profile length, and an integer linear program formulation. For the latter problem we show it is NP-hard and give an integer linear program formulation that scales to practical problem instance sizes. We assess the efficiency and quality of our algorithms on simulated instances. Availability https://github.com/raphael-group/CNT-ILP
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ISSN:1748-7188
1748-7188
DOI:10.1186/s13015-017-0103-2